OUTCOME MEASURES: Pain-free patients at end of treatment; treatment failure (proportion of patients stopping the assigned treatment for lack of effect on pain); number of days with no, mild, moderate, or severe pain; quality of life; number of days on nonsteroidal anti-inflammatory drugs; number of drug prescriptions; VAS1 and VAS2 scores; quality of life and psychosocial findings; and reduction of disc protrusion on magnetic resonance imaging.

METHODS: Manipulations or simulated manipulations were done 5 days per week by experienced chiropractors, with a number of sessions which depended on pain relief or up to a maximum of 20, using a rapid thrust technique. Patients were assessed at admission and at 15, 30, 45, 90, and 180 days. At each visit, all indicators of pain relief were used.

RESULTS: A total of 64 men and 38 women aged 19–63 years were randomized to manipulations (53) or simulated manipulations (49). Manipulations appeared more effective on the basis of the percentage of pain-free cases (local pain 28 vs. 6%; p CONCLUSIONS: Active manipulations have more effect than simulated manipulations on pain relief for acute back pain and sciatica with disc protrusion.

From the FULL TEXT Article:

Introduction

Acute back pain and sciatica are major sources of disability,
with impairment of daily living activities. Many
medical interventions are available but the results are conflicting. [1] Spinal manipulations are widely used. [2] The
rationale for manipulation includes reduction of a bulging
disc, correction of disc displacement, release of adhesive
fibrosis surrounding prolapsed discs or facet joints and entrapped
synovial folds or plicae, inhibition of nociceptive
impulses, relaxation of hypertonic muscles, and unbuckling
displaced motion segments. [3, 4] However, a systematic
review of randomized clinical trials did not unanimously
demonstrate the efficacy of spinal manipulations, some reports
concluding that there is moderate evidence that spinal
manipulations are effective for pain relief [5] and have
better short-term efficacy than spinal mobilization and detuned
diathermy [6], and others that there is no evidence
that spinal manipulative therapy is superior to standard
treatments. [7] Results are also conflicting for chronic spinal
pain. [5–9] These contradictory findings can be partly
explained by differences in study design and poor methodological
quality. [10, 11] In addition, some groups of patients
seemed to benefit from manipulations, but these
subgroups cannot be consistently identified. Also, the
long-term effects of manipulation are poorly defined and
the effects of spinal manipulations on the outcome of acute
back pain and sciatica with protruding discs are unknown.

We therefore conducted a randomized double-blind clinical
trial to assess the short- and long-term impact of spinal
manipulations on acute back pain and sciatica in a cohort of
patients with lumbar disc protrusion. The aim was to assess
the benefit, if any, of spinal manipulations as opposed to
sham manipulations in this target group, expressed in terms
of pain reduction and treatment continuation.

Material and methods

Study population and selection criteria

Included were consecutive ambulatory patients age 18
to 65 years, seen between February 9, 1999 and October
27, 2000 in two medical rehabilitation centers in and near
Rome (Celio Hospital and Istituto Chirurgico Ortopedico
Traumatologico [ICOT]). To be included, each individual
had to report acute low back pain (LBP) of moderate to
severe intensity (5 or higher on a 10 cm visual analog
scale [VAS]) [12], moderate to severe radiating pain to
one leg (5 or higher on a VAS), and magnetic resonance
imaging (MRI) evidence of disc protrusion with or without
disc degeneration in the spinal segments involved in
pain.

Acute LBP was defined as pain for less than 10 days in
a patient who had been pain-free in the previous 3 months.
Evoked local and radiating pain was assessed using the 10–
point VAS (VAS1 and VAS2, respectively). We used a
10–cm line where 0 cm corresponded to ‘‘no pain’’ and
10 cm to ‘‘unbearable pain’’. The patients responded by
placing a mark somewhere along the line. Local pain was
identified by palpation and percussion on the lumbosacral
spine and the sciatic notch in order to identify trigger
points. Radiating pain was evoked by specific clinical tests,
including straight leg raising [13] and Wasserman [14]
maneuver (hyperextension of the hip with the patient in
the prone position with the knee flexed at 90; this maneuver
evokes pain by stimulating the L2–L4 roots).

Disc abnormalities were classified according to the Modic
classification [15] and subjects with 4A herniated disc (protrusion
with an intact annulus) were included in the study.

A patient was excluded if at least one of the following
conditions was satisfied: body mass index O30; lumbar
scoliosis O20; lower limb length difference more than
1.5 cm on plane X-rays; spondylolisthesis, previous spinal
surgery, and diabetic neuropathy to rule out alternative pain
sources; severe osteoporosis (bone mineral density [quantitative
ultrasound on densitometry] more than 2.5 SD lower
than the mean of normal age-matched individuals) and
metabolic disease causing osteopenia, for which spinal manipulative
therapy is contraindicated; clinical, electrophysiological,
or radiological findings suggesting a lesion
requiring surgery; herniated disc classified as 4B (extrusion
with rupture of either the annulus or the posterior longitudinal
ligament, or both) or 4C (rupture of the annulus and
the posterior longitudinal ligament with sequestration of
a disc fragment in the spinal canal); history of chronic
LBP. Patients were also excluded if they had already received
spinal manipulation, to avoid possible blinding failure,
and if they refused to give written informed consent.
Electrophysiological tests were done only in diabetic patients
in order to exclude diabetic neuropathy; bone mineral
density was assessed only in patients with X-ray signs of
osteoporosis.

Baseline assessment

At admission, every eligible patient was interviewed directly
and given a complete physical examination and,
where indicated, blood biochemical, hematological, electrophysiological,
and radiological tests to check the exclusion
criteria, and to collect the main demographic and
clinical details. The interview included the collection of data
about pain (site, number of segments, aggravating factors),
VAS1 and VAS2 scores, the patient’s psychological
profile, and quality of life. The psychological profile was
scored using the Italian translation of the Kellner rating
scale. [16] The Italian version of the Rand 36-Item Health
Survey (Short Form-36) [17] was used to assess quality of
life.

MRI findings of disc protrusion were obtained at admission
and verified at the end of the follow-up period using
the same procedure and equipment. MRI readings were
done by the same radiologist in each center. Disc protrusion
changes were assessed using the Modic criteria. [15]
Reduction of disc protrusion was measured by a shift to
a lower Modic category.

Randomization and treatment modalities

The patients were randomized blindly to active or simulated
manipulations using computer-generated lists. The
allocation sequence was generated at the "Mario Negri"
Institute in Milan, the trial coordinating center, using two
lists, one for each center. Participants were enrolled by
local investigators from the two centers. Each investigator
informed the trial coordinating center by telephone of each
eligible patient and received the assigned treatment
immediately.

Individuals assigned active manipulations were treated
according to a pre-planned 30–day protocol with a number
of sessions that depended on pain relief or up to a maximum
of 20. Sessions were scheduled 5 days per week, each lasting
5 minutes for active and simulated manipulations.
Active manipulations consisted of examining the range of
motion in the back, followed by soft tissue manipulations
and brisk rotational thrusting away from the greatest restriction,
as described by Herbst [18] and Plaugher. [19]
The aim of manipulation of the spinal column was to restore
the physiological motor unit movement (a motor unit
consists of two vertebrae, disc, and surrounding structures).
With the patient sitting, the pertinent segment of the spine
was examined and assessed by motion palpation in order to
determine the joint hypo-hypermobility. The patient was
then laid on one side, with arms folded and thighs flexed.
The chiropractor faced the patient and made contact with
one hand at the level of the patient’s shoulder and the other
at the level of the vertebral motor unit to be mobilized.
The slack was then taken up and a quick, precise, wellcontrolled
movement was imparted with either a push or
pull, always toward the pain-free direction.

Subjects randomized to simulated manipulations received
soft muscle pressing apparently similar to manipulations
but not following any specific patterns and not
involving rapid thrusts. Active and simulated manipulations
were done by two experienced chiropractors, one at each
center, who both held U.S. Doctor of Chiropractic degrees
and had received the same formal training.

Follow-up

After admission, each patient received an ad hoc diary in
which to record the days of pain during the 30–day treatment
period, number and type of nonsteroidal anti-inflammatory
drugs, and number of drug prescriptions. Opiates
and steroids were not allowed. In the diaries, pain days
were indicated in separate categories according to severity,
which was coded arbitrarily as absent, mild, moderate, or
severe (the latter including severe, very severe, and unbearable
pain) specifying any radiation to a leg. Patients were
also assessed for pain relief with a series of clinical indicators
(see below) at the scheduled visits (at 15, 30, 45, 90,
and 180 days). Assessors (physiatrists), who were different
from the investigators who enrolled the participants, were
blind to the assigned treatments.

Outcome measures (Table 1)

The primary outcome measures included the number of
patients becoming pain-free at the end of treatment and
treatment failure, defined by the number of patients stopping
the assigned treatment because of no benefit (no reduction
of pain). Secondary outcome measures included
number of days with pain of any severity, number of days
with at least moderate pain, mean number of days on nonsteroidal
anti-inflammatory drugs, mean number of drug
prescriptions, number of patients experiencing less severe
pain, number of patients becoming pain-free at each follow-
up, changes in the VAS1 and VAS2 scores at each follow-up, mean SF-36 and Kellner scores, and mean number
of cases experiencing at least a reduction of disc protrusion
as shown by MRI (at 45 days).

Statistical analysis was done using the chi-square or
Fisher exact test, Student t test, or the Mann-Whitney test,
and analysis of variance, as appropriate. The choice of
parametric or nonparametric tests was dictated by the results
of a test for normality of data. Multivariate repeated
measures and analysis of variance was used to test the effect
of time, treatment, and the interaction time by treatment
on the VAS1 and VAS2 scores. All analyses were
done on an intention-to-treat basis. Standard statistical software
packages (SPSS 10.0 and SAS 6.09) were used. All
reported p values are two-tailed. No adjustment for multiplicity
of reporting was considered because it increases
the type II errors for associations that are not null. [20]

Sample size and power

Sample size was calculated under the assumption that
20% of patients randomized to simulated manipulations
and 50% of those randomized to manipulations (30% absolute
difference) would be pain-free at the end of treatment.
The study was also powered to detect a 30% absolute difference
in the proportion of treatment failures at the end
of follow-up (simulated manipulations 60%; manipulations
30%). On this basis, the minimum number of patients to be
enrolled in each treatment arm would be 40 with at least
80% power and 5% significance. Allowing for a 20%
drop-out rate, 100 patients had to be recruited.

Ethical and regulatory issues

The study was approved by the Institutional Review
Board of the "Centro Studi di Patologia Vertebrale", a
nonprofit orthopedic and rehabilitation institution. The procedures
followed were in accordance with the ethical
standards of the Committee on Human Experimentation
of the institutions involved.

Results

During the study period, 485 ambulatory patients presented
to the two study centers with at least moderate acute
back pain. Of these, 383 were not randomized as they were
ineligible (326) or because they declined participation
(Figure 1). One hundred and two patients were randomized
to manipulation (53) or simulated manipulation (49). The
sample included 64 men and 38 women age 19 to 63 years
(mean 43.1), who presented lumbar or lumbosacral pain
caused by disc protrusion. The two treatment groups were
fairly well balanced for local and referred pain intensity
(VAS1 and VAS2) (Table 2). The mean (SD) number of sessions
was 12.8 (4.8) for active manipulation and 13.0 (4.5)
for simulated manipulation.

At the end of follow-up a significant difference was present
between active and simulated manipulations in the percentage
of cases becoming pain-free (local pain 28% vs.
6%, p!.005; radiating pain 55% vs. 20%, p!.0001)
(Table 3).

There were only six patients discontinuing treatment or
lost to follow-up (manipulation 5; simulated manipulation
1) (Fig. 1). Of these, only two (manipulation 1; simulated
manipulation 1) were dissatisfied with treatment. There
were no missing data from patients completing follow-up,
who were fully compliant with the completion of their
diaries.

Differences between active and simulated manipulations
were also found for total number of days with pain (23.6 vs.
27.4; p!.005) and total number of days with moderate or
severe pain (13.9 vs. 17.9; p!.05) (Table 3). Active manipulations
were followed by reduction of radiating pain,
with no significant trends, and by a lower (nonsignificant)
number of days on, and prescriptions of, nonsteroidal
anti-inflammatory drugs.

At first follow-up (day 15), patients receiving manipulation
had a lower mean VAS1 score than patients given simulated
manipulation (mean difference 0.8) (Figure 2A). The
mean difference increased slightly at subsequent visits,
with peaks (1.8) at days 45 and 90. The pattern was the
same for the VAS2 scores (Figure 2B). These differences were
significant by multivariate analysis both for VAS1 (F 17.6;
p
There were no statistically significant differences in the
Kellner symptom scores and SF-36 scores in the two groups
(Table 4). Follow-up MRI confirmed disc protrusion in all
patients with signs of disc degeneration (34 patients receiving
manipulations and 42 simulated manipulations). MRI
findings were unchanged from baseline (see Table 1).

Table 4.
Spinal manipulations for
acute back pain and sciatica
with disc protrusion

Discussion

Patients receiving active manipulations enjoyed significantly
greater relief of local and radiating acute LBP, spent
fewer days with moderate-to-severe pain, and consumed
fewer drugs for the control of pain. However, only few
patients withdrew from treatment, with no significant differences
for active and simulated manipulations. We assigned
a pragmatic a priori difference between treatment
and control groups, on the basis that withdrawal before concluding
treatment would be a robust measure of efficacy.
On that basis, active manipulations did not appear superior
to simulated manipulations. The low rate of withdrawal from
treatment for both active and sham manipulations is important
in this context, as simulated manipulations can be assimilated
to massage, which may have some effect on LBP.

Although no adjustments were made for multiple observations,
the possibility of chance findings can be excluded
by the statistical significance of the results, even considering
the variety of secondary outcome measures. These findings
are in keeping with other reports comparing spinal
manipulation to other or no treatment [21–26], but contrast
with some well-conducted randomized clinical trials which
did not find manipulations consistently better than other
treatments in patients with acute back pain. [27–30] However,
some found good results in selected subgroups, defined
by the duration of symptoms [28] and the response
to straight leg raising. [31] Thus, manipulations may relieve
acute back pain and sciatica with disc protrusion, although
the results of subgroup analyses must be interpreted with
caution.

Interestingly, pain was also significantly reduced in patients
given simulated manipulations, starting from day 30
(Fig. 2) with a smaller difference between treatments when
comparing day 90 with day 180. Although, as noted above,
simple massage may be helpful in relieving LBP, this finding
supports the assumption that, even when disc protrusion
appears unchanged at follow-up, as observed in the present
study, acute back pain is self-limiting and its natural history
is toward regression in a few weeks in a large proportion of
cases. [32, 33] This could also explain why the majority of
patients continued the planned treatment (either true or
simulated), despite unchanged psychiatric symptoms and
quality of life measures, under the assumption of a perceived
benefit.

Despite the positive findings, the study has two major
limitations. First, in the absence of an exit interview there
is no certainty that our patients were truly blinded as to group
involvement. However, the exclusion of patients undergoing
previous manipulations and the low rate of withdrawal in
both treatment arms is against the possibility of unmasking.
Second, the external validity of our results is limited by the
fact that only two institutions were involved, and by the
treatment of pain with disc protrusion. Thus, this study needs
to be replicated in other settings to verify its findings.

Acknowledgments

We are grateful for statistical advice from Dr. Irene
Floriani, and to Ms. Susanna Franceschi for typing the manuscript.
Special thanks go to the physiatrists (Dr. Roberto
Lucchesi, Dr. Matilde Celentano, Dr. Marzio Simonelli,
and Dr. Cosimo Buccolieri) for the clinical work, the radiologists
(Dr. Massimo Derme and Dr. Carlo Ottonello) for
their help and advice, and the chiropractors (Dr. Domenico
Bonaduce and Dr. Wayne Zilker) (affiliations: Static
Centers of Rome and "ICOT" Latina, Italy).